Precise structural and synaptic relationships in the outer plexiform layer (OPL) of the retina underlie the first steps in visual processing. The cellular mechanisms responsible for the development of this circuitry, however, are unknown. The proposed research will investigate the role of horizontal cells in OPL assembly during early postnatal development in the mouse retina. The hypothesis that GABAergic signaling by horizontal cells regulates OPL development will be tested in Aim 1 by using genetic strategies to eliminate GABA synthesis by these neurons. In Aim 2, the hypothesis that horizontal cells provide additional cues necessary for OPL assembly will be tested via the generation of a conditional knockout mouse in which horizontal cells can be specifically ablated during early development. In both aims, the consequences for photoreceptor, bipolar cell, and horizontal cell maturation will be assessed. Identifying the influences that sculpt and constrain the assembly of this circuitry is relevant to degenerative diseases in which the laminar structure of the outer retina is lost. A greater understanding of OPL development will also provide insight into mechanisms guiding the establishment of precise cell-cell connectivity throughout the nervous system. [unreadable] [unreadable]